Assessing Gene Therapy to Upregulate Three Longevity-Associated Genes in Mice
In this study, we developed gene therapies based on 3 longevity associated genes: fibroblast growth factor 21 (FGF21), αKlotho, soluble form of mouse transforming growth factor-β receptor 2 (sTGFβR2). The gene therapies were delivered using adeno-associated viruses, and we explored their ability to mitigate 4 age-related diseases: obesity, type II diabetes, heart failure, and renal failure.
Individually and combinatorially, we applied these therapies to disease-specific mouse models and found that this set of diverse pathologies could be effectively treated and in some cases, even reversed with a single dose. We observed a 58% increase in heart function in ascending aortic constriction ensuing heart failure, a 38% reduction in α-smooth muscle actin (αSMA) expression, and a 75% reduction in renal medullary atrophy in mice subjected to unilateral ureteral obstruction and a complete reversal of obesity and diabetes phenotypes in mice fed a constant high-fat diet. Crucially, we discovered that a single formulation combining 2 separate therapies into 1 was able to treat all 4 diseases. These results emphasize the promise of gene therapy for treating diverse age-related ailments and demonstrate the potential of combination gene therapy that may improve health span and longevity by addressing multiple diseases at once.
Source: Fight Aging! - Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
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